Ca(2+) binding protein frequenin mediates GDNF-induced potentiation of Ca(2+) channels and transmitter release

C Y Wang; F Yang; X He; A Chow; J Du; J T Russell; B Lu

doi:10.1016/s0896-6273(01)00434-2

Ca(2+) binding protein frequenin mediates GDNF-induced potentiation of Ca(2+) channels and transmitter release

Neuron. 2001 Oct 11;32(1):99-112. doi: 10.1016/s0896-6273(01)00434-2.

Authors

C Y Wang¹, F Yang, X He, A Chow, J Du, J T Russell, B Lu

Affiliation

¹ Laboratory of Cellular and Synaptic Neurophysiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.

PMID: 11604142
DOI: 10.1016/s0896-6273(01)00434-2

Abstract

Molecular mechanisms underlying long-term neurotrophic regulation of synaptic transmission and plasticity are unknown. We report here that long-term treatment of neuromuscular synapses with glial cell line-derived neurotrophic factor (GDNF) potentiates spontaneous and evoked transmitter release, in ways very similar to presynaptic expression of the Ca(2+) binding protein frequenin. GDNF enhances the expression of frequenin in motoneurons, and inhibition of frequenin expression or activity prevents the synaptic action of GDNF. GDNF also facilitates Ca(2+) influx into the nerve terminals during evoked transmission by enhancing Ca(2+) currents. The effect of GDNF on Ca(2+) currents is blocked by inhibition of frequenin expression, occluded by overexpression of frequenin, and is selective to N-type Ca(2+) channels. These results identify an important molecular target that mediates the long-term, synaptic action of a neurotrophic factor.

MeSH terms

Animals
Antibodies / pharmacology
Calcium / metabolism*
Calcium Channels, N-Type / metabolism*
Calcium-Binding Proteins / genetics
Calcium-Binding Proteins / immunology
Calcium-Binding Proteins / metabolism*
Cells, Cultured
Electrophysiology
Gene Expression / physiology
Glial Cell Line-Derived Neurotrophic Factor
Motor Neurons / cytology
Motor Neurons / physiology
Muscle Fibers, Skeletal / cytology
Muscle Fibers, Skeletal / physiology
Nerve Growth Factors*
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / immunology
Nerve Tissue Proteins / metabolism*
Neuronal Calcium-Sensor Proteins
Neuropeptides
Neurotransmitter Agents / metabolism*
Oligonucleotides, Antisense / pharmacology
Presynaptic Terminals / metabolism
RNA, Messenger / analysis
Synaptic Transmission / physiology
Xenopus
Xenopus Proteins*

Substances

Antibodies
Calcium Channels, N-Type
Calcium-Binding Proteins
Glial Cell Line-Derived Neurotrophic Factor
Nerve Growth Factors
Nerve Tissue Proteins
Neuronal Calcium-Sensor Proteins
Neuropeptides
Neurotransmitter Agents
Oligonucleotides, Antisense
RNA, Messenger
Xenopus Proteins
frequenin calcium sensor proteins
Calcium